Advances in modeling gastric intestinal metaplasia: a comprehensive review of experimental models and mechanistic insights.

Epithelial cells within the gastric corpus mucosa exhibit a dynamic response to injury, characterized by alterations in gene transcription, cellular phenotype, and tissue organization, collectively termed metaplasia. Among these changes, gastric intestinal metaplasia (GIM) represents one of the most prevalent precancerous lesions associated with intestinal-type gastric cancer (GC). This pathological progression typically evolves through a sequence of stages: chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia, and ultimately, GC. A deeper understanding of GIM is crucial for advancing diagnostic and therapeutic strategies in GC management. Despite its clinical significance, progress in elucidating the underlying mechanisms of GIM has been limited, primarily due to the lack of reliable and reproducible animal models that accurately recapitulate this condition. This review systematically examines the existing mouse, rat, and organoid models utilized for GIM research, providing critical insights into various methodological approaches and potential mechanisms. Specifically, we investigate five pivotal aspects of pyloric metaplasia and GIM: Helicobacter pylori infection, bile acid induction, chemical agent interventions, transgenic technologies, and gastric organoids. Through this comprehensive analysis, we aim to establish a robust foundation for future research initiatives focused on unraveling the molecular mechanisms driving GIM development and formulating effective prevention and treatment strategies.